The purpose of the present work is to elucidate the pattern of lipid metabolism occurring in the axon and the nature of the membranes involved. Studied will be conducted to determine how this metabolism is altered under those conditions in which nerve impulse propagation and/or axonal transport are blocked. Axonal transport of phospholipids will be studied in order to understand the relationships in the metabolism of the perikaryal supplied lipids to those formed locally. An independent study will be undertaken to determined if axon-associated enzymes appear earlier in development in spinal nerves than Schwann-cell and myelination-related enzymes. Squid giant axon will be studied and comparisons will be made between lipid metabolism occurring in this invertebrate axon and mammalian peripheral nerve axons. These above studies will utilize autoradiographic and biochemical approaches already employed in this laboratory. The autoradiographic approaches will be extensive, employing a wide variety of potential lipid precursors, yet quantitative. Quantitative analyses will be aimed at determining the extent of axonal lipid formation (both with respect to overall level and to fiber population) and the fate of axonally formed lipids, e.g. turnover from synthetic sites. Under conditions in which axonal functions are impaired, changes in lipid metabolism will be characterized both as to radioactive products formed (biochemical) and sites of formation and subsequent metabolism (autoradiographic). Biochemical studies, with rat sciatic nerve (nerve ligation paradigm) and squid giant axon as enzyme sources, will be conducted to determined the capacities of the axon for phospholipid metabolism and the specific nature of the membrane sites where this metabolism is located. These studies, employing enzyme assays, will complement the autoradiographic studies in the localization of lipid products to axon will elicit experiments to confirm that responsible enzyme are present in axoplasm and/or axolemma.